The purpose of this work is to understand the cellular and molecular mechanisms of neoplastic progression of respiratory tract epithelial cells. The specific aims of the study are: (1) to define the stages in neoplastic progression; (2) to determine the role of mutagenesis in progression, i.e., in the transition of one transformation stage to the next; (3) to determine the role of tumor promoters in progression, whether they act mainly through inductive or through selective mechansims; and (4) to determine the effect of carcinogen dose on neoplastic progression of epithelial cells. These studies employ a cell culture model for the quantitation of preneoplastic and neoplastic conversion of rat tracheal epithelial cells following treatment with chemical carcinogens and tumor promoters.